Primate breeding season: photoperiodic regulation in captive Lemur catta.
Under natural light in Portland, Oreg., captive ring-tailed lemurs (Lemur catta) experience a breeding season that differs by nearly half a year from the season in Madagascar. A series of experimental day length changes from 1971 to 1974 demonstrated the ability of both temperate and tropical photoperiod cycles to induce estrous cycles in quiescent animals. After photoperiodic activation, most impregnated females failed to resume estrous cycles even after infant separations unless they received additional photoperiod changes. Unimpregnated females, on the other hand, showed no significant decline in the incidence of estrous cycles under prolonged exposure to a constant day length regimen (12.OL:12.OD) for over a year.


Direct creation of a photoinduced metallic structure and its optical properties in the terahertz frequency region.
We investigate the surface electromagnetic characteristics of a photoinduced periodical structure using the attenuated total reflection (ATR) technique in the terahertz frequency region. A wire grating structure is generated at the surface of a silicon prism by irradiation with a spatially modulated, ultrafast pulsed laser. A characteristic minimum due to the excitation of surface waves is observed in the ATR spectrum. The depth profile of the photoinduced carrier layer is also studied. We confirm that the photoinduced structure has metallic properties. This fabrication technique will be developed as a simple method to create "active" structures.


Radiotelemetric analysis of the effects of prevailing wind direction on Mormon cricket migratory band movement.
During outbreaks, flightless Mormon crickets [Anabrus simplex Haldeman (Orthoptera: Tettigoniidae)] form large mobile groups known as migratory bands. These bands can contain millions of individuals that march en masse across the landscape. The role of environmental cues in influencing the movement direction of migratory bands is poorly understood and has been the subject of little empirical study. We examined the effect of wind direction on Mormon cricket migratory band movement direction by monitoring the local weather conditions and daily movement patterns of individual insects traveling in bands over the same time course at three close, but spatially distinct sites. Although weather conditions were relatively homogeneous across sites, wind directions tended to be more variable across sites during the morning hours, the period during which directional movement begins. Migratory bands at different sites traveled in distinctly different directions. However, we failed to find any evidence to suggest that the observed variation in migratory band movement direction was correlated with local wind direction at any time during the day. These results support the notion that the cues mediating migratory band directionality are likely to be group specific and that a role for landscape-scale environmental cues such as wind direction is unlikely.


LATS kinase-mediated CTCF phosphorylation and selective loss of genomic binding.
Chromatin topological organization is instrumental in gene transcription. Gene-enhancer interactions are accommodated in the same CTCF-mediated insulated neighborhoods. However, it remains poorly understood whether and how the 3D genome architecture is dynamically restructured by external signals. Here, we report that LATS kinases phosphorylated CTCF in the zinc finger (ZF) linkers and disabled its DNA-binding activity. Cellular stress induced LATS nuclear translocation and CTCF ZF linker phosphorylation, and altered the landscape of CTCF genomic binding partly by dissociating it selectively from a small subset of its genomic binding sites. These sites were highly enriched for the boundaries of chromatin domains containing LATS signaling target genes. The stress-induced CTCF phosphorylation and locus-specific dissociation from DNA were LATS-dependent. Loss of CTCF binding disrupted local chromatin domains and down-regulated genes located within them. The study suggests that external signals may rapidly modulate the 3D genome by affecting CTCF genomic binding through ZF linker phosphorylation.


Relationship between types of common channel and development of biliary tract cancer in pancreaticobiliary maljunction.
The incidence of biliary tract cancer development is high among patients with pancreaticobiliary maljunction. However, there have been no reports published evaluating the incidence of development of biliary tract cancers in pancreaticobiliary maljunction based on the morphology of the common channel at the junction of the bile and pancreatic ducts. We evaluated between types of common channel and development of biliary tract cancers in pancreaticobiliary maljunction. During the last 21 years, we have experienced 78 patients with pancreaticobiliary maljunction. Of those patients, 44 adult patients, whose morphologic types of common channel were identified by cholangiography, were enrolled in this study. The dilatation patterns of the common channel were classified into 3 types: A type (moderately dilated type), B type (markedly dilated type), and C type (non-dilated type). Evaluated items included the length and dilation patterns of the common channel, incidence of development of biliary tract cancers and proliferative activity in the biliary tract epithelium. Seventeen patients had a common channel shorter than 20 mm, while 27 had a common channel of 20 mm or longer. Eleven patients with a common channel of 20 mm or longer had development of bile tract cancers. The dilation patterns of the common channel were classified as A (11 patients), B (16 patients) and C type (17 patients). Amylase levels in the biliary tract were higher in patients with A and B type than in patients with the C type. Development of gallbladder cancer was observed in 6 patients with A, 2 patients with B and one patient with C, while development of bile duct cancer was observed in 2 patients with C and one patient with B. The PCNAL.I. of the biliary epithelium was higher in patients with A, B and C type in descending order. The incidence of development of biliary tract cancer was higher in patients with common channel of 20 mm or longer. The proliferative activity in the biliary epithelium was accelerated in patients with A type, together with a high incidence of development of gallbladder cancer.


[Mapping the sequences, preferentially bound with the nuclear matrix, on human chromosome 19].
A plasmid library (400 clones) of the human chromosome 19 sequences selectively binding to nuclear matrix was obtained and characterized. Approximately 50% clones contained DNA sequences specific for human chromosome 19. Over 90% of these sequences represented matrix attachment regions (MARs). Eight MARs were localized to the chromosome 19 physical map.


Mutation of GALNTL5 gene identified in patients diagnosed with asthenozoospermia.
Asthenozoospermia is commonly observed in infertile men. However, very few causative gene mutations have been identified because an efficient detection method has not been established. We previously identified a patient with asthenozoospermia carrying a heterozygous point deletion in GALNTL5 by detecting an abnormal reduction in the abundance of GALNTL5 and other marker proteins. To identify other mutations in GALNTL5, we screened sperm samples from 208 infertile men mainly diagnosed with asthenozoospermia using the same method, and conducted next-generation sequencing. Consequently, another case of GALNTL5 mutation was detected only in sperm at a low frequency but not in the somatic blood cells of a patient diagnosed with asthenozoospermia. In this patient, sperm motility improved and the mutation disappeared at 2 years after the first observation. In this man, carrying a heterozygotic deficiency of GALNTL5, the swim-up method was useful to concentrate the spermatozoa without mutation. Intracytoplasmic sperm injection of the selected motile spermatozoa into oocytes of the patient's partner resulted in successful conception, and a female child was safely delivered. These results suggest the feasibility of our approach for the screening and treatment of asthenozoospermia associated with GALNTL5 mutation.


Crystal structure of insecticidal delta-endotoxin from Bacillus thuringiensis at 2.5 A resolution.
The structure of the delta-endotoxin from Bacillus thuringiensis subsp. tenebrionis that is specifically toxic to Coleoptera insects (beetle toxin) has been determined at 2.5 A resolution. It comprises three domains which are, from the N- to C-termini, a seven-helix bundle, a three-sheet domain, and a beta sandwich. The core of the molecule encompassing all the domain interfaces is built from conserved sequence segments of the active delta-endotoxins. Therefore the structure represents the general fold of this family of insecticidal proteins. The bundle of long, hydrophobic and amphipathic helices is equipped for pore formation in the insect membrane, and regions of the three-sheet domain are probably responsible for receptor binding.


Dorsal Augmentation with Homologous Rib.
Dorsal augmentation grafts are used to reconstruct and raise the nasal dorsum in patients with dorsal saddling due to trauma, infection, or previous nasal surgery, as well as in patients with a narrow, congenitally low, and/or wide dorsum. Alloplastic implants and various biomaterials are available for grafting, each with advantages and disadvantages. Although autologous septal cartilage is a preferable and often convenient source of cartilage, it is frequently not sufficient for large volume dorsal augmentation, nor is it available in patients who have had septoplasty, infection, previous rhinoplasty with grafting, or significant trauma. Ear cartilage may be used but it is difficult to make homogenous and smooth, and dorsal irregularities can be seen in the long term especially in thin-skinned patients. For these reasons, we frequently use irradiated costal cartilage from tissue banks as our grafting source, thereby eliminating the morbidity of harvesting the patient's own rib. Proper surgical techniques, the use of antibiotics, and proper sculpting and placement of the cartilage limits complications such as warping, resorption, infection, and extrusion. Irradiated homograft costal cartilage grafts have been used successfully in large numbers of patients with long-term follow-up with low complication rates and serve as a welcome alternative to harvesting a patient's rib cartilage.


Subtotal ostectomy of impinging dorsal spinous processes in 23 standing horses.
To (1) describe a safe, efficient surgical technique for subtotal ostectomy (SO) of diseased dorsal spinal processes (DSP) of the caudal thoracic vertebrae with the horse standing and (2) report outcome. Case series. Horses (n = 23) with reduced performance caused by impingement of the DSP of the caudal thoracic vertebrae. Affected DSP were resected through a dorsal median incision with the horse standing, sedated, and the surgical site desensitized with local anesthetic. Radiography was used to confirm removal of impinging bone before wound closure. No serious complications occurred. Outcome was obtained for 22 horses. At <1 year, 19 horses (86%) returned to full athletic function, 2 horses (9%) improved but had failed to return to full function, 1 horse had no improvement. At >1 year, 2 horses that had returned to full athletic function were unable to function at full capacity; 1 was considered improved, but the other had not improved. Athletic function in 1 horse improved 6 months after surgery, but at 2.5 years was no better than before surgery. Subtotal ostectomy of impinging DSPs can be performed with good results with the horse standing.


Taking a patient history: the role of the nurse.
History taking is a key component of patient assessment, enabling the delivery of high-quality care. Understanding the complexity and processes involved in history taking allows nurses to gain a better understanding of patients' problems. Care priorities can be identified and the most appropriate interventions commenced to optimise patient outcomes.


Formaldehyde kinetics and bacteriology in dialyzers.
The kinetics of formaldehyde washout in new and reused dialyzers with 2% (w/v) and 4% formaldehyde solution was studied. Using a standard method of rinsing, the concentration of formaldehyde decreases exponentially, but the rate of decrease and the steady-state level depends on the type of dialyzer. The residual quantity of formaldehyde using a 4% solution is more than twice that seen with a 2% solution in similar dialyzers. Bacteriological tests on water-adapted, formaldehyde-resistant organisms indicate that a significant proportion of these organisms can survive a 4-hr incubation with 4% formaldehyde at 20 degrees C. However, increasing the temperature of incubation to 40 degrees C or the addition of ethanol up to 8% (v/v) improved the bacteriological efficacy of formaldehyde. Under these conditions, a 1% formaldehyde solution allows eradication of all organisms tested. Similar results were observed in multiple-use dialyzers inoculated with the same organisms. There was no effect of incubation at 40 degrees C on the in vitro clearance determinations of new and reused dialyzers.


Expression of PTEN and its pseudogene PTENP1, and promoter methylation of PTEN in non-tumourous thymus and thymic tumours.
Mutation or promoter methylation of the phosphatase tensin homologue deleted on chromosome 10 tumour suppressor gene (PTEN) promotes some cancers. Moreover, PTENP1 (PTEN pseudogene) transcript regulates PTEN expression and is thought to be associated with tumourigenesis in some cancers. Here, we investigated PTEN expression in thymic epithelium and thymic epithelial tumours. Immunohistochemical analysis of PTEN was performed on two non-tumourous thymus (NT) samples, 33 thymomas (three type A, eight type AB, 11 type B1, six type B2, and five type B3), and four thymic carcinomas (TCs). In 16 cases (two NT, three A, five B1, two B2, one B3 and three TC), analyses of mutations, promoter methylation and comparisons of PTEN mRNA and PTENP1 transcripts were undertaken using PCR-direct sequencing, methylation-specific PCR, and reverse-transcription real-time PCR after target cell collection with laser microdissection. PTEN protein was not immunohistochemically detected in NT epithelium or types B1 or B2 thymoma cells, but was expressed in type A thymoma and carcinoma cells. Neither PTEN mutations nor promoter methylation were detected in any samples. Statistical analysis revealed that PTEN mRNA expression was highest in NT epithelium and lowest in type A thymoma cells. PTENP1 transcript expression did not significantly differ among NT, thymoma and TC samples. We speculated that NT epithelium and types B1/B2 thymoma cells have a mechanism of PTEN translation repression and/or acceleration of protein degradation, whereas type A thymoma cells exhibit transcriptional repression of PTEN mRNA and accelerated translation and/or protein accumulation.


Family Childcare Types and Conduct Problem Behaviors in Young Children: The Mediation Role of Caregiver-Child Interaction.
Background: Previous studies have demonstrated the impacts of genetic, family, and community factors on child conduct problems (CPs). However, little is understood regarding the association between family childcare types and child conduct problem behaviors, as well as whether and to what extent caregiver-child interaction mediates the above association. Methods: 9,289 children first entering kindergartens in the Longhua New District of Shenzhen, China were enrolled in this cross-sectional study. Primary caregivers were invited to fulfill a self-administered structured questionnaire containing data regarding socio-demographics, family childcare types, caregiver-child interaction, and child conduct problem behaviors (measured by the Conners' Conduct Problem Subscale). A series of multiple logistic and linear regression models were employed to assess the associations among family childcare, caregiver-child interaction, and child conduct problem behaviors. Results: Family childcare types other than by parents together (i.e., mother alone, mother with others, grandparents, or changing caregivers) were all significantly associated with higher risks of conduct problem behaviors in young children (adjusted ORs ranged from 2.18 to 2.55, and adjusted βs ranged from 0.043 to 0.073; all p < 0.05), after adjusting for confounders including child age, gender, parental education level, parental age at pregnancy, marital status, and family income. The following family childcare types (mother alone, or grandparents, or changing caregivers) vs. the childcare by parents together showed significant relative indirect effects on conduct problem behaviors through caregiver-child interaction, indicating the significant mediation effect of caregiver-child interaction on the above associations. Mediation of caregiver-child interaction on the effect of being cared by mother with others relative to care by parents together on child conduct problem behaviors was yet non-significant. Conclusions: Family childcare types other than by parents together are associated with increased risks for conduct problem behaviors in young children. Caregiver-child interaction may function as a potential mediator for the above association.


Brainstem auditory-evoked potentials in iron-deficiency anemia.
Slight-to-moderate impairments may be observed in mental and motor developments of infants with iron- deficiency anemia. Brainstem auditory-evoked potentials provide a noninvasive means of examining the auditory aspect of the central nervous system functions. In this study the effect of iron-deficiency anemia on auditory functions was investigated by using brainstem auditory-evoked potentials. Brainstem auditory-evoked potentials of the 20 iron-deficient infants were not significantly different from those of the control group that included 20 healthy age-matched infants. Furthermore, there was not a statistically significant difference between the brainstem auditory-evoked potentials of the study group performed before and 3 months after oral iron therapy. Although we could not demonstrate a hearing loss in infants with moderate iron-deficiency anemia in this study, the relationship between severe iron-deficiency anemia and hearing loss or auditory dysfunction remains to be determined.


Effect of cassava starch coating on quality and shelf life of fresh-cut pineapple (Ananas comosus L. Merril cv "Pérola").
This research studied the influence of treatment with ascorbic acid, citric acid, and calcium lactate dipping and cassava starch edible coatings on quality parameters and shelf life of fresh-cut pineapple in slices during 12 d at 5 °C. After previous tests, the treatments selected for this study were samples dipped into antibrowning solution with 0.5% of ascorbic acid and 1% of citric acid, with and without 2% of calcium lactate and coated with 2% of cassava starch suspensions. Changes in weight loss, juice leakage, mechanical properties (stress at failure), color parameters (L* and H*), ascorbic acid content, sensory acceptance, and microbial growth of fruits were evaluated. Samples only treated with antibrowning agents were used as control. Edible coatings with and without calcium lactate were efficient in reducing weight loss, juice leakage, and maintaining firmness during storage. However, these samples showed more browning and the ascorbic acid content was reduced. All treatments presented good sensory acceptance (scores above 6). The determining factor of shelf life of pineapple slices was the microbial spoilage. A shelf life of 8 d was obtained for pineapple slices only treated with antibrowning agents. On the other hand, coated samples showed a reduced shelf life of 7 d and higher yeast and mold growth. Thus, although cassava starch coatings were efficient in reducing respiration rate, weight loss, and juice leakage and maintained mechanical properties, these treatments were not able to increase the shelf life of minimally processed pineapple. Practical Application: Pineapple fruit is highly appreciated for its aroma, flavor, and juiciness, but its immediate consumption is difficult. Therefore, pineapple is a potential fruit for minimal processing. However, shelf life of fresh-cut pineapple is very limited by changes in color, texture, appearance, off-flavors, and microbial growth. The use of edible coatings as gas and water vapor barrier and antibrowning agents can extend the storage time and maintain the quality of fresh-cut produce. Cassava starch and alginate coatings are alternative to preserve minimally processed pineapples without changing the quality parameters of fresh fruit. Thus, this study is useful for consumers and fresh-cut industry interested in knowing factors affecting shelf life and quality of fresh-cut pineapple.


A quantitative model of traffic between plasma membrane and secondary lysosomes: evaluation of inflow, lateral diffusion, and degradation.
We present here a mathematical model that accounts for the various proportions of plasma membrane constituents occurring in the lysosomal membrane of rat fibroblasts (Draye, J.-P., J. Quintart, P. J. Courtoy, and P. Baudhuin. 1987. Eur. J. Biochem. 170: 395-403; Draye, J.-P., P. J. Courtoy, J. Quintart, and P. Baudhuin. 1987. Eur. J. Biochem. 170:405-411). It is based on contents of plasma membrane markers in purified lysosomal preparations, evaluations of their half-life in lysosomes and measurements of areas of lysosomal and plasma membranes by morphometry. In rat fibroblasts, structures labeled by a 2-h uptake of horseradish peroxidase followed by a 16-h chase (i.e., lysosomes) occupy 3% of the cellular volume and their total membrane area corresponds to 30% of the pericellular membrane area. Based on the latter values, the model predicts the rate of inflow and outflow of plasma membrane constituents into lysosomal membrane, provided their rate of degradation is known. Of the bulk of polypeptides iodinated at the cell surface, only 4% reach the lysosomes every hour, where the major part (integral of 83%) is degraded with a half-life in lysosomes of integral to 0.8 h. For specific plasma membrane constituents, this model can further account for differences in the association to the lysosomal membrane by variations in the rate either of lysosomal degradation, of inflow along the pathway from the pericellular membrane to the lysosomes, or of lateral diffusion.


Long-term outcome of esthesioneuroblastoma: hyams grade predicts patient survival.
Object Esthesioneuroblastoma (ENB) is a rare malignant neuroendocrine tumor originating from the olfactory neuroepithelium in the cribriform plate. Controversy still exists regarding the role of pathologic grading (Hyams grade) in prognostication. This study was undertaken to describe our experience with ENB and assess the role of pathologic grading in patient outcome. Methods This was a retrospective, single-institution experience, including 109 patients with ENB treated at our institution from 1962 to 2009. Multivariate analysis was performed utilizing Cox regression analysis models utilizing age, gender, modified Kadish stage, and Hyams grade. Results Mean age was 49 ± 16 (median 50) years at presentation (range 12 to 90 years). Median follow up was 5.1 years. All-cause mortality was significantly influenced by Hyams grading in univariate (p = 0.04) and multivariate (p = 0.02) analysis, in addition to proven prognostic factors, Kadish staging, lymph node metastasis, and age. Median survival was 9.8 years compared with 6.9 years with low (grade 1 to 2) versus high (grade 3 to 4) Hyams grade. Median overall survival was 7.2 ± 0.7 years. Conclusion ENB has a variable outcome, which is primarily prognosticated by the extent of involvement at presentation (Kadish stage and lymph node metastasis) and higher Hyams pathologic grade.


Posthumous reproduction and the meanings of autonomy.
In recent years there has been considerable debate over the legal and ethical issues associated with posthumous reproduction. This article analyses recent cases and legal regulation of reproductive technologies in Australia. The issues associated with posthumous reproduction are explored through a consideration of the nature of an individual's interest in their reproductive material. The suitability of a property-based model as a means of conceptualising interests in reproductive material is explored. The article concludes that the issues in this area need to be analysed in terms of autonomy interests that are understood relationally.


CD8+CD60+ T cells, cells expressing epsilon specific mRNA and Th1/Th2 cytokines in cord blood and at 7 months of age.
IgE levels in cord blood have been investigated as predictors of atopy, but no definitive findings have been made. Other factors, including cells and/or cytokines may serve as predictors of this disease. Cord blood and peripheral blood was obtained at birth and at 7 months of age, respectively, from children (n = 2) with a family history of allergy. Cells in cord blood and peripheral blood were phenotyped and levels of serum immunoglobulins (IgM, IgG, IgA and IgE) were determined. In addition, placentas from these pregnancies were obtained and stained for IgE+ cells and CD8+CD60+ T cells. We found immunoglobulin levels were within normal ranges although IgE levels were negligible in cord blood and at 7 months of age. Similar numbers of CD8+ T cells and CD19+ B cells were detected in cord blood and at 7 months of age. However, CD4+ T cells increased (twofold) and CD16+/CD56+ natural killer precursor cells decreased (twofold) at 7 months of age. CD8+ T cells in their cord blood and at 7 months of age comprised of >50% CD8+CD60+ T cells. Cord blood cells expressed epsilon-specific mRNA and mRNA for interleukin-2 (IL-2), IL-4, IL-10 and interferon-gamma (IFN-gamma) but not IL-6. At 7 months of age, peripheral blood mononuclear cells expressed epsilon-specific mRNA and mRNA for all cytokines. In the placental membrane, we detected IgE+ cells, while CD8+CD60+ T cells were detected in the chorionic villi. CD8+CD60+ T cells, cells expressing epsilon-specific and IL-6-specific mRNA may contribute to the pathobiology and provide important prognostic indicators of atopy.


Colloidal Gold-Mediated Delivery of Bleomycin for Improved Outcome in Chemotherapy.
Nanoparticles (NPs) can be used to overcome the side effects of poor distribution of anticancer drugs. Among other NPs, colloidal gold nanoparticles (GNPs) offer the possibility of transporting major quantities of drugs due to their large surface-to-volume ratio. This is while confining these anticancer drugs as closely as possible to their biological targets through passive and active targeting, thus ensuring limited harmful systemic distribution. In this study, we chose to use bleomycin (BLM) as the anticancer drug due to its limited therapeutic efficiency (harmful side effects). BLM was conjugated onto GNPs through a thiol bond. The effectiveness of the chemotherapeutic drug, BLM, is observed by visualizing DNA double strand breaks and by calculating the survival fraction. The action of the drug (where the drug takes effect) is known to be in the nucleus, and our experiments have shown that some of the GNPs carrying BLM were present in the nucleus. The use of GNPs to deliver BLM increased the delivery and therapeutic efficacy of the drug. Having a better control over delivery of anticancer drugs using GNPs will establish a more successful NP-based platform for a combined therapeutic approach. This is due to the fact that GNPs can also be used as radiation dose enhancers in cancer research.


Nutritional, environmental and economic impacts of ultra-processed food consumption in Australia.
To quantify the full life cycle impacts of ultra-processed foods (UPF) for key environmental, economic and nutritional indicators to identify trade-offs between UPF contribution to broad-scope sustainability. Using 24-h dietary recalls along with an input-output database for the Australian economy, dietary environmental and economic impacts were quantified in this national representative cross-sectional analysis. Food items were classified into non-UPF and UPF using the NOVA system, and dietary energy contribution from non-UPF and UPF fractions in diets was estimated. Thereafter, associations between nutritional, environmental and economic impacts of non-UPF and UPF fractions of diets were examined using a multi-dimensional nutritional geometry representation. National Nutrition and Physical Activity Survey 2011-2012 of Australia. Respondents (n 5344) aged > 18 years with 1 d of 24-h dietary recall data excluding respondents with missing values and outlier data points and under reporters. Australian diets rich in UPF were associated with reduced nutritional quality, high greenhouse gas emissions, energy use, and increased employment and income associated with the food supply chains. The environmental and economic impacts associated with the UPF portion of diets become more distinct when the diets are standardised to average protein recommendation. Increased consumption of UPF has socio-economic benefits, but this comes with adverse effects on the environment and public health. Consideration of such trade-offs is important in identifying policy and other mechanisms regarding UPF for establishing healthy and sustainable food systems.


Effect of common medications on the expression of SARS-CoV-2 entry receptors in liver tissue.
Besides lung drastic involvement, SARS-CoV-2 severely affected other systems including liver. Emerging epidemiological studies brought the attentions towards liver injury and impairment as a potential outcome of COVID19. Angiotensin-converting enzyme 2 (ACE2) and Transmembrane serine protease (TMPRSS2) are the main cell entry receptors of SARS-CoV-2. We have tested the ability of medications to regulate expression of SARS-CoV-2 receptors. Understanding that may reflect how such medications may affect the level of infectivity and permissibility of the liver following COVID-19. Using transcriptomic datasets, Toxicogenomic Project-Genomics Assisted Toxicity Evaluation System (Open TG-GATEs) and GSE30351, we have tested the ability of ninety common medications to regulate COVID-19 receptors expression in human primary hepatocytes. Most medications displayed a dose-dependent change in expression of receptors which could hint at a potentially more pronounced change with chronic use. The expression level of TMPRSS2 was increased noticeably with a number of medications such as metformin. Within the analgesics, acetaminophen revealed a dose-dependent reduction in expression of ACE2, while non-steroidal anti-inflammatory drugs had mixed effect on receptors expression. To confirm the observed effects on primary human hepatocytes, rat hepatocyte treatments data was obtained from DrugMatrix toxicogenomic database (GSE57805), which showed a similar ACE2 and TMPRSS2 expression pattern. Treatment of common co-morbidities often require chronic use of multiple medications, which may result in an additive increase in the expression of ACE2 and TMPRSS2. More research is needed to determine the effect of different medications on COVID-19 receptors.


Payer database and geospatial analysis to evaluate practice patterns in treating allergy in North Carolina.
The objective of this study was to characterize the delivery of allergy care in North Carolina using a large payer charge database and visualization techniques. Geospatial database analysis. North Carolina State claims database. Medical data from the 2013 FAIR Health National Private Insurance Claims (FH NPIC) database for North Carolina was mined for CPT codes and charges for allergy testing, and for the preparation and provision of allergen immunotherapy. Provider and patient variables were analyzed. Analyses were performed to compare differences in allergy care delivery. A visualization strategy complemented the analytic approach. 162,037 CPT charge entries were analyzed. Allergy-immunology specialists were the most common provider specialty to perform allergy immunotherapy treatments (68.9%, p<0.05). Among other specialties, there were no significant differences between specialists performing immunotherapy when comparing otolaryngology, family practice, and internal medicine (16.3%; 4.6%; 2.6%; p>0.05). Providers with an M.D. degree were the most common provider type. The three most commonly treated diagnoses were allergic rhinitis variants. Females were more likely to receive allergy treatments versus males (55.9% vs. 51.5%; p<0.001), and were more likely to receive allergy testing (65.3% vs. 34.7%: p<0.005). Internal medicine providers charged higher than any other specialist type (p<0.05) for allergy immunotherapy. Using a large payer database coupled with visualization techniques was an efficient approach to characterizing the state-wide provision patterns of allergy diagnostic and therapy services in North Carolina. This first tier approach to efficiently exploring questions and describing populations is valuable.


Habitat connectivity shapes urban arthropod communities: the key role of green roofs.
The installation of green roofs, defined here as rooftops with a shallow soil cover and extensive vegetation, has been proposed as a possible measure to mitigate the loss of green space caused by the steady growth of cities. However, the effectiveness of green roofs in supporting arthropod communities, and the extent to which they facilitate connectivity of these communities within the urban environment is currently largely unknown. We investigated the variation of species community composition (beta diversity) of four arthropod groups with contrasting mobility (Carabidae, Araneae, Curculionidae, and Apidae) on 40 green roofs and 40 extensively managed green sites on the ground in the city of Zurich, Switzerland. With redundancy analysis and variation partitioning, we (1) disentangled the relative importance of local environmental conditions, the surrounding land cover composition, and habitat connectivity on species community composition, (2) searched for specific spatial scales of habitat connectivity for the different arthropod groups, and (3) discussed the ecological and functional value of green roofs in cities. Our study revealed that on green roofs community composition of high-mobility arthropod groups (bees and weevils) were mainly shaped by habitat connectivity, while low-mobility arthropod groups (carabids and spiders) were more influenced by local environmental conditions. A similar but less pronounced pattern was found for ground communities. The high importance of habitat connectivity in shaping high-mobility species community composition indicates that these green roof communities are substantially connected by the frequent exchange of individuals among surrounding green roofs. On the other hand, low-mobility species communities on green roofs are more likely connected to ground sites than to other green roofs. The integration of green roofs in urban spatial planning strategies has great potential to enable higher connectivity among green spaces, so that eventually even communities of low-mobility species become connected. Furthermore, improving the design of green roofs (composition and configuration of vegetation and soil types) could enhance the ecological value, particularly for low-mobility species.


TBC1D24 truncating mutation resulting in severe neurodegeneration.
Recessive TBC1D24 gene mutations have been described in two families: an Italian family afflicted with familial infantile myoclonic epilepsy, and an Arab family with focal epilepsy and intellectual disability syndrome. The patients in the Italian family were compound heterozygous for two mutations, whereas those in the Arab family were homozygotes. All three mutations were missense and were determined to be loss of function. We conducted a gene search in a family we previously reported with a severe, lethal epileptic encephalopathy mapping at 16pter-p13.3. Exome sequencing and subsequent Sanger sequencing of TBC1D24 exons were conducted. Sanger sequencing was used to determine the structures of novel mRNA isoforms. The abundance of mRNA isoforms was assessed via real-time quantitative PCR. A homozygous two-base pair deletion leading to premature termination and two novel TBC1D24 transcript isoforms were identified. Isoform 1 is predominant in the brain whereas isoform 2 is predominant in non-neural tissues, except for muscle. The very severe phenotype in our patients can be attributed to mutation severity; however, the mutation does not affect isoform 2, whereas the three previously reported mutations do. These findings expand the spectrum of the TBC1D24 mutation phenotype and the transcript isoforms.


Prevalence of Multiple Sclerosis in the City of Volta Redonda - Rio De Janeiro, Brazil Using the Capture-Recapture Method.
Multiple sclerosis (MS) prevalence in Latin America was estimated in some regions and it was found to range from 0.75 to 30/100,000. The reasons for variation in rates of prevalence around the world still are not clear, but there are environmental and genetic explanations to this phenomenon. This study aimed at estimating the MS prevalence in Volta Redonda, Brazil. Three sources of cases ascertainment were used and the method of capture-recapture was applied for assessing the corrected prevalence in the city of Volta Redonda in November 2012. The capture-recapture method uses data from incomplete lists and allows calculating the number of unregistered cases. Data were analyzed using a log-linear model. A total of 40 MS cases was found by withdrawing overlaps of sources and it was estimated that a total number of 40 cases (95% CI 13.5-118.8) were not detected by the sources. The corrected prevalence of MS was, then, 30.7/100,000. Our study was the first in Brazil to use the capture-recapture method to assess the prevalence of MS, demonstrating the highest prevalence rate so far. It is necessary to perform other similar studies and in other regions of the country using the same method for a better evaluation of the true prevalence of MS our country.


Evidence and practice in spine registries.
We performed a systematic review and a survey in order to (1) evaluate the evidence for the impact of spine registries on the quality of spine care, and with that, on patient-related outcomes, and (2) evaluate the methodology used to organize, analyze, and report the "quality of spine care" from spine registries. To study the impact, the literature on all spinal disorders was searched. To study methodology, the search was restricted to degenerative spinal disorders. The risk of bias in the studies included was assessed with the Newcastle-Ottawa scale. Additionally, a survey among registry representatives was performed to acquire information about the methodology and practice of existing registries. 4,273 unique references up to May 2014 were identified, and 1,210 were eligible for screening and assessment. No studies on impact were identified, but 34 studies were identified to study the methodology. Half of these studies (17 of the 34) were judged to have a high risk of bias. The survey identified 25 spine registries, representing 14 countries. The organization of these registries, methods used, analytical approaches, and dissemination of results are presented. We found a lack of evidence that registries have had an impact on the quality of spine care, regardless of whether intervention was non-surgical and/or surgical. To improve the quality of evidence published with registry data, we present several recommendations. Application of these recommendations could lead to registries showing trends, monitoring the quality of spine care given, and ultimately improving the value of the care given to patients with degenerative spinal disorders.


Effect of Exposure to Positive Images of Dentistry on Dental Anxiety among 7 to 12 Years Old Children.
To evaluate the effect of exposure to positive images of dentistry on dental anxiety among 7 to 12 years old children. Controlled trial. Assessment of anxiety and analysis of data were conducted blind to experimental condition. Assessment of anxiety was carried out in the waiting room prior intervention, postintervention into the operatory during the treatment and again after the completion of treatment. Anticipatory anxiety was recorded by Venham's picture test (VPT). Sixty children of 7 to 12 years age group. PARTICIPANTS were randomly assigned to one of two conditions. In both conditions the participant was asked to look at photographs for 2 minutes in the waiting area prior to their appointment. The intervention consisted of viewing positive images of dentistry and dental treatment (study group), the (control group) consisted of neutral images. The assessment of anticipatory dental anxiety was made blind to experimental condition and statistical analysis was conducted blind to group membership. Anticipatory anxiety assessed by the VP T. A total of 60 subjects participated in the study and were equally and randomly allotted to study group (positive image) and control group (neutral image). The mean anxiety score found at waiting area before intervention, after intervention (OPD) and postoperative was statistically significant in study group. Post hoc comparison of anxiety score in study group showed high statistical significance. Positive dental images have an effect on reducing anxiety as compared to neutral images when measured by the VPT. How to cite this article: Gangwal RR, Badjatia SR, Dave BH. Effect of Exposure to Positive Images of Dentistry on Dental Anxiety among 7 to 12 Years Old Children. Int J Clin Pediatr Dent 2014;7(3):176 -179.


SkiVis: Visual Exploration and Route Planning in Ski Resorts.
Optimal ski route selection is a challenge based on a multitude of factors, such as the steepness, compass direction, or crowdedness. The personal preferences of every skier towards these factors require individual adaptations, which aggravate this task. Current approaches within this domain do not combine automated routing capabilities with user preferences, missing out on the possibility of integrating domain knowledge in the analysis process. We introduce SkiVis, a visual analytics application to interactively explore ski slopes and provide routing recommendations based on user preferences. In collaboration with ski guides and enthusiasts, we elicited requirements and guidelines for such an application and propose different workflows depending on the skiers' familiarity with the resort. In a case study on the resort of Ski Arlberg, we illustrate how to leverage volunteered geographic information to enable a numerical comparison between slopes. We evaluated our approach through a pair-analytics study and demonstrate how it supports skiers in discovering relevant and preference-based ski routes. Besides the tasks investigated in the study, we derive additional use cases from the interviews that showcase the further potential of SkiVis, and contribute directions for further research opportunities.


Alvocidib (flavopiridol) for the treatment of chronic lymphocytic leukemia.
Alvocidib, which has orphan drug designation in chronic lymphocytic leukemia (CLL) from the FDA and the EMA, is a plant-derived semisynthetic flavone that acts as a cyclin-dependent kinase inhibitor. It induces apoptosis in CLL cells in vitro and was introduced into clinical trials in CLL as an intravenous infusion in 1997, which proved disappointing. Since the drug avidly binds to plasma proteins, higher serum concentrations were required for clinical antileukemia activity than those suggested by in vitro studies. Subsequent studies utilizing bolus plus infusional doses revealed significant activity against CLL, even in patients with unfavorable characteristics. However, significant toxicity including high rates of major tumor lysis syndrome, cytokine release syndrome and secretory diarrhea were also observed. The chemistry, pharmacodynamics, pharmacokinetics and metabolism of alvocidib are briefly discussed and phase I-II studies in CLL are discussed in detail. To date, no phase III studies in CLL have been reported. A number of much less toxic drugs with similar efficacy against CLL both with and without unfavorable cytogenetics have come to market. Furthermore, enthusiasm for the development of alvocidib as a single agent for the treatment of CLL has waned, primarily due to its toxicity.


Karyotype asymmetry: again, how to measure and what to measure?
One of the most popular, cheap and widely used approaches in comparative cytogenetics - especially by botanists - is that concerning intrachromosomal and interchromosomal karyotype asymmetry. Currently, there is no clear indication of which method, among the many different ones reported in literature, is the most adequate to infer karyotype asymmetry (especially intrachromosomal), above all in view of the criticisms recently moved to the most recent proposal published. This work addresses a critical review of the methods so far proposed for estimation of karyotype asymmetry, using both artificial and real chromosome datasets. It is shown once again how the concept karyotype of asymmetry is composed by two kinds of estimation: interchromosomal and intrachromosomal asymmetries. For the first one, the use of Coefficient of Variation of Chromosome Length, a powerful statistical parameter, is here confirmed. For the second one, the most appropriate parameter is the new Mean Centromeric Asymmetry, where Centromeric Asymmetry for each chromosome in a complement is easily obtained by calculating the difference of relative lengths of long arm and short arm. The Coefficient of Variation of Centromeric Index, strongly criticized in recent literature, is an additional karyological parameter, not properly connected with karyotype asymmetry. This shows definitively what and how to measure to correctly infer karyotype asymmetry, by proposing to couple two already known parameters in a new way. Hopefully, it will be the basic future reference for all those scientists dealing with cytotaxonomy.


High occurrence of Pacearchaeota and Woesearchaeota (Archaea superphylum DPANN) in the surface waters of oligotrophic high-altitude lakes.
We carried out a regional survey on the archaea composition from surface waters of > 300 high-altitude Pyrenean lakes (average altitude 2300 m, pH range 4.4-10.1) by 16S rRNA gene tag sequencing. Relative Archaea abundances ranged between 0% and 6.3% of total prokaryotes amplicons in the polymerase chain reaction (PCR) mixture, and we detected 769 operational taxonomic units (OTUs; grouped at 97% identity) that split into 13 different lineages, with altitude and pH having a significant effect on the community composition. Woesearchaeota and Pacearchaeota (formerly Euryarchaeota DHVEG-6 cluster) dominated the data set (83% of total OTUS), showed a high occurrence (presence in c. 75% of the lakes) and had relative abundances significantly and positively correlated with the phylogenetic diversity of bacterial communities. Micrarchaeota-Diapherotrites (formerly Euryarchaeota MEG cluster), Methanomicrobia, Thermoplasmata and ammonia-oxidizing thaumarchaeota (AOA) showed relative abundances between 1% and 3% and occurrences between 14% and 26%. Minor lineages were SM1K20, Aenigmarchaeota (formerly Euryarchaeota DSEG cluster), Methanobacteria, Bathyarchaeota and SCG. Environmental preferences substantially differed among lineages, with Aenigmarchaeota and Methanomicrobia having the largest habitat breadth, and Thermoplasmata, AOA and Micrarchaeota having the smallest. Pacearchaeota and Woesearchaeota had been mostly reported from saline habitats and sediments, but surface waters of oligotrophic alpine lakes are suitable environments for such ecologically spread and genetically diverse archaeal lineages.


Direct reprogramming of fibroblasts into myocytes to reverse fibrosis.
Heart disease is a major cause of morbidity and mortality worldwide. The low regenerative capacity of adult human hearts has thus far limited the available therapeutic approaches for heart failure. Therefore, new therapies that can regenerate damaged myocardium and improve heart function are urgently needed. Although cell transplantation-based therapies may hold great potential, direct reprogramming of endogenous cardiac fibroblasts, which represent more than half of the cells in the heart, into functional cardiomyocytes in situ may be an alternative strategy by which to regenerate the heart. We and others demonstrated that functional cardiomyocytes can be directly generated from fibroblasts by using several combinations of cardiac-enriched factors in mouse and human. In vivo gene delivery of cardiac reprogramming factors generates new cardiac muscle and improved heart function after myocardial infarction in mouse. This article reviews recent progress in cardiac reprogramming research and discusses the perspectives and challenges of this new technology for future regenerative therapy.


Improving sexual health communication between older women and their providers: how the integrative model of behavioral prediction can help.
Talking about sexual health can be a challenge for some older women. This project was initiated to identify key factors that improve communication between aging women and their primary care providers. A sample of women (aged 60+) completed an online survey regarding their intent to communicate with a provider about sexual health. Using the integrative model of behavioral prediction as a guide, the survey instrument captured data on attitudes, perceived norms, self-efficacy, and intent to communicate with a provider about sexual health. Data were analyzed using structural equation modeling. Self-efficacy and perceived norms were the most important factors predicting intent to communicate for this sample of women. Intent did not vary with race, but mean scores of the predictors of intent varied for African American and White women. Results can guide practice and intervention with ethnically diverse older women who may be struggling to communicate about their sexual health concerns.


Reconstitution of LDL with lipophilic fluorescein derivatives: quantitative analysis of the receptor activity of human lymphocytes.
Low density lipoprotein (LDL), the major cholesterol transport protein in human plasma, consists of an apolar core of cholesteryl esters surrounded by a polar shell containing phospholipids, unesterified cholesterol and protein. In the current paper we report the absorption and fluorescence spectra of members of a new class of lipophilic fluorescein derivatives which were designed to be reconstituted into the core of LDL in place of the native cholesteryl esters. One of these derivates, cholesteryl 12-O-[methyl 3-O-methyl-5' (6')-carboxyfluorescein]ricinoleyl carbonate (MMC) was reconstituted into the core of LDL. The resultant fluorescent reconstituted LDL was used in conjunction with flow cytometry to quantify the LDL receptor activity of fresh blood lymphocytes derived from normal individuals and from patients with the heterozygous and homozygous forms of familial hypercholesterolemia (FH). The LDL receptor activities of the heterozygous and homozygous FH lymphocytes were approximately 37% and 1% of normal, respectively. LDL reconstituted with these lipophilic fluorescein derivatives will be valuable in studying LDL metabolism and may be useful for the diagnosis of FH.


Use of gender distribution in routine surveillance data to detect potential transmission of gastrointestinal infections among men who have sex with men in England.
Detecting gastrointestinal (GI) infection transmission among men who have sex with men (MSM) in England is complicated by a lack of routine sexual behavioural data. We investigated whether gender distributions might generate signals for increased transmission of GI pathogens among MSM. We examined the percentage male of laboratory-confirmed patient-episodes for patients with no known travel history for 10 GI infections of public health interest in England between 2003 and 2013, stratified by age and region. An adult male excess was observed for Shigella spp. (annual maximum 71% male); most pronounced for those aged 25-49 years and living in London, Brighton and Manchester. An adult male excess was observed every year for Entamoeba histolytica (range 59.8-76.1% male), Giardia (53.1-57.6%) and Campylobacter (52.1-53.5%) and for a minority of years for hepatitis A (max. 69.8%) and typhoidal salmonella (max. 65.7%). This approach generated a signal for excess male episodes for six GI pathogens, including a characterised outbreak of Shigella among MSM. Stratified analyses by geography and age group were consistent with MSM transmission for Shigella. Optimisation and routine application of this technique by public health authorities elsewhere might help identify potential GI infection outbreaks due to sexual transmission among MSM, for further investigation.


Technical requirements for cultured meat production: a review.
Environment, food, and disease have a selective force on the present and future as well as our genome. Adaptation of livestock and the environmental nexus, including forest encroachment for anthropological needs, has been proven to cause emerging infectious diseases. Further, these demand changes in meat production and market systems. Meat is a reliable source of protein, with a majority of the world population consumes meat. To meet the increasing demands of meat production as well as address issues, such as current environmental pollution, animal welfare, and outbreaks, cellular agriculture has emerged as one of the next industrial revolutions. Lab grown meat or cell cultured meat is a promising way to pursue this; however, it still needs to resemble traditional meat and be assured safety for human consumption. Further, to mimic the palatability of traditional meat, the process of cultured meat production starts from skeletal muscle progenitor cells isolated from animals that proliferate and differentiate into skeletal muscle using cell culture techniques. Due to several lacunae in the current approaches, production of muscle replicas is not possible yet. Our review shows that constant research in this field will resolve the existing constraints and enable successful cultured meat production in the near future. Therefore, production of cultured meat is a better solution that looks after environmental issues, spread of outbreaks, antibiotic resistance through the zoonotic spread, food and economic crises.


The Effects of Body Position on Trochanteric Soft Tissue Thickness-Implications for Predictions of Impact Force and Hip Fracture Risk During Lateral Falls.
Trochanteric soft tissue thickness (TSTT) is a protective factor against fall-related hip fractures. This study's objectives were to determine: (1) the influence of body posture on TSTT and (2) the downstream effects of TSTT on biomechanical model predictions of fall-related impact force (Ffemur) and hip fracture factor of risk. Ultrasound was used to measure TSTT in 45 community-dwelling older adults in standing, supine, and side-lying positions with hip rotation angles of -25°, 0°, and 25°. Supine TSTT (mean [SD] = 5.57 [2.8] cm) was 29% and 69% greater than in standing and side-lying positions, respectively. The Ffemur based on supine TSTT (3380 [2017] N) was 19% lower than the standing position (4173 [1764] N) and 31% lower than the side-lying position (4908 [1524] N). As factor of risk was directly influenced by Ffemur, the relative effects on fracture risk were similar. While less pronounced (<10%), the effects of hip rotation angle were consistent across TSTT, Ffemur, and factor of risk. Based on the sensitivity of impact models to TSTT, these results highlight the need for a standardized TSTT measurement approach. In addition, the consistent influence of hip rotation on TSTT (and downstream model predictions) support its importance as a factor that may influence fall-related hip fracture risk.


[A case of pathological complete response to lt. Lateral lymph node metastasis from lower rectal cancer by S-1 combined neoadjuvant chemoradiotherapy].
A 54-year-old man presented with an enlarged left (lt) lateral lymph node (LLN), which was detected by magnetic resonance imaging (MRI) and positron emission tomography/computed tomography (PET-CT). Endoscopic examination of the colon revealed the presence of a type 1 tumor, 20mm in diameter, in the lower rectum; the tumor was diagnosed as a well-differentiated adenocarcinoma (tub1). The patient received combined neoadjuvant chemoradiotherapy (nCRT)with S- 1 for treatment of the rectal cancer and LLN metastasis (MP, T2N3M0, Stage IIIb). S-1 was administered orally at a dose of 120 mg/day on days 1-14, and 22-35; a total dose of 45 Gy was delivered (1.8 Gy/day, for 25 days). Upon nCRT, there was a remarkable reduction in the tumor size, the primary tumor receded, and the LLN decreased from 16 mm to 8 mm in diameter. The maximum standardized uptake value (SUVmax) also decreased from 3.8 to 1.9 on PET-CT. Six weeks after nCRT, ultralow anterior resection and bilateral lymph node dissections were performed. Histopathological examination showed a partial presence of cancer cells in the scarred primary tumor; however, no viable cancer cells were observed in the lt. LLN.


Systemic and global toxicities of head and neck treatment.
The increased use of aggressive, combined modality therapy for the treatment of head and neck cancer has resulted in a marked increase in acute and late adverse effects. The acute effects of therapy have long been appreciated; however, it is now being recognized that the late effects of therapy result in a significant symptom burden, diminished functional capacity and decreased quality of survivorship. Furthermore, head and neck cancer has historically been considered a locoregional disease that is treated predominantly with locoregional therapy. It is now recognized that there are systemic effects of therapy that need to be considered. Potential systemic effects of therapy include: fatigue, weight loss, nutritional deficiencies, altered physical functioning and mood disorders. It is important for clinicians to be aware of these late effects in order to provide patients with appropriate support services and referrals. This paper examines the global and systemic effects of therapy.


Impaired vasoconstriction of peripheral cutaneous blood flow in Type 1 diabetic patients following food ingestion.
Abnormalities in cutaneous blood flow (CBF) in otherwise healthy subjects with Type 1 diabetes mellitus (DM) have been demonstrated in response to local insults to the skin. To investigate whether defects also occurred in response to a regular daily activity, CBF was measured with laser Doppler flowmetry (LDF), before and 20 min after starting a mixed meal in 13 male Type 1 DM subjects with no clinical evidence of neuropathy, nephropathy or macroangiopathy and compared to 7 non-diabetic controls. Diabetic subjects and controls were of similar age and body mass index (mean +/- SD, 33.7 +/- 7.4 vs 37.1 +/- 9.2 years and 25.2 +/- 2.9 vs 24.5 +/- 2.9 kg m(-2), respectively). In subjects with DM, HbA1c was 8.3 +/- 0.6% (normal range 4-5.5%) and duration of diabetes was 18 (8-38) years, median (range). Following a mixed meal the CBF fell in the controls by 36% (24 to 56), median (range), compared to 3% (-5 to 18) in Type 1 DM subjects, P < 0.0005. These results show there is a normal physiological fall in CBF following food ingestion which is attenuated in Type 1 DM. These abnormalities of vasoconstriction in the peripheral microcirculation are present after 8 years of diabetes and precede the development of clinically apparent neuropathy or vascular disease.


Myeloperoxidase serves as a redox switch that regulates apoptosis in epithelial ovarian cancer.
Resistance to apoptosis is a key feature of cancer cells and is believed to be regulated by nitrosonium ion (NO(+))-induced S-nitrosylation of key enzymes. Nitric oxide (NO), produced by inducible nitric oxide synthase (iNOS), is utilized by MPO to generated NO(+). We sought to investigate the expression of myeloperoxidase (MPO) and iNOS in epithelial ovarian cancer (EOC) and determine their effect on S-nitrosylation of caspase-3 and its activity as well as apoptosis. MPO and iNOS expression were determined using immunofluorescence in SKOV-3 and MDAH-2774 and EOC tissue sections. S-nitrosylation of caspase-3 and its activity, levels of MPO and iNOS, as well as apoptosis, were evaluated in the EOC cells before and after silencing MPO or iNOS genes with specific siRNA probes utilizing real-time RT-PCR, ELISA, and TUNEL assays. MPO and iNOS are expressed in EOC cell lines and in over 60% of invasive EOC cases with no expression in normal ovarian epithelium. Indeed, silencing of MPO or iNOS gene expression resulted in decreased S-nitrosylation of caspase-3, increased caspase-3 activity, and increased apoptosis but with a more significant effect when silencing MPO. MPO and iNOS are colocalized to the same cells in EOC but not in the normal ovarian epithelium. Silencing of either MPO or iNOS significantly induced apoptosis, highlighting their role as a redox switch that regulates apoptosis in EOC. Understanding the mechanisms by which MPO functions as a redox switch in regulating apoptosis in EOC may lead to future diagnostic tools and therapeutic interventions.


Use of a novel hybrid vascular graft for sutureless revascularization of the renal arteries during open thoracoabdominal aortic aneurysm repair.
The aim of this study was to assess the safety and short-term effectiveness of a novel hybrid vascular graft used to address renal revascularization during open thoracoabdominal aortic aneurysm (TAAA) repair, performing a sutureless distal anastomosis. Between 2012 and 2013, 25 patients (16 men; mean age, 66 ± 8 years) underwent revascularization of one (24 patients) or both (one patient) renal arteries with the Gore Hybrid Vascular Graft (GHVG; W. L. Gore and Associates, Flagstaff, Ariz) during open TAAA repair. Specific indications included remote location of the ostium of the renal artery, severe atherosclerotic wall degeneration, focal dissection, and stenosis. All surviving patients underwent computed tomography angiography and follow-up visit at 1 month. Preoperative characteristics, intraoperative data, and short-term results were compared with those of 49 concurrent TAAA patients operated on within the same period by standard renal revascularization (SRR) techniques. All GHVG target renal vessels (26 of 26) were successfully revascularized without technical concerns. No significant differences were found between GHVG and SRR groups in preoperative and intraoperative data, except for a relative prevalence of aortic dissection (28% vs 6%; P = .026) and renal artery stenosis (44% vs 12%; P = .003) in the GHVG group and for intraoperative renal bare stenting that was predominantly used in the SRR group (12% vs 28%; P = .036). The 30-day mortality was 4% in both groups. Postoperative acute renal failure (doubling of creatinine level and creatinine level >3.0 mg/dL) occurred in two GHVG patients (8%) and seven SRR patients (14%; P = NS). Perioperative peak decrease of estimated glomerular filtration rate was lower in the GHVG group (26 ± 18 mL/min/1.73 m(2) vs 37 ± 22 mL/min/1.73 m(2); P = .034). At 1-month computed tomography angiography, renal artery patency was 92% for the GHVG vessels, 91% for the contralateral to GHVG renal vessels, and 92% for the SRR group arteries. No GHVG-related complications requiring reintervention or cases of new-onset renal failure requiring dialysis were observed at follow-up. Renal revascularization during open TAAA repair by the GHVG with distal sutureless anastomosis is feasible, especially in cases of aortic dissection, remote location of the renal vessel, and severe atherosclerotic disease of the ostium. Short-term results are satisfactory, at least comparable to those of SRR. Larger series and longer follow-up are needed to assess clinical advantages and durability of this new device.


Identifying human disease genes: advances in molecular genetics and computational approaches.
The human genome project is one of the significant achievements that have provided detailed insight into our genetic legacy. During the last two decades, biomedical investigations have gathered a considerable body of evidence by detecting more than 2000 disease genes. Despite the imperative advances in the genetic understanding of various diseases, the pathogenesis of many others remains obscure. With recent advances, the laborious methodologies used to identify DNA variations are replaced by direct sequencing of genomic DNA to detect genetic changes. The ability to perform such studies depends equally on the development of high-throughput and economical genotyping methods. Currently, basically for every disease whose origen is still unknown, genetic approaches are available which could be pedigree-dependent or -independent with the capacity to elucidate fundamental disease mechanisms. Computer algorithms and programs for linkage analysis have formed the foundation for many disease gene detection projects, similarly databases of clinical findings have been widely used to support diagnostic decisions in dysmorphology and general human disease. For every disease type, genome sequence variations, particularly single nucleotide polymorphisms are mapped by comparing the genetic makeup of case and control groups. Methods that predict the effects of polymorphisms on protein stability are useful for the identification of possible disease associations, whereas structural effects can be assessed using methods to predict stability changes in proteins using sequence and/or structural information.


Insights into origins and function of the unexplored majority of the reductive dehalogenase gene family as a result of genome assembly and ortholog group classification.
Organohalide respiring bacteria (OHRB) express reductive dehalogenases for energy conservation and growth. Some of these enzymes catalyze the reductive dehalogenation of chlorinated and brominated pollutants in anaerobic subsurface environments, providing a valuable ecosystem service. Dehalococcoides mccartyi strains have been most extensively studied owing to their ability to dechlorinate all chlorinated ethenes - most notably carcinogenic vinyl chloride - to ethene. The genomes of OHRB, particularly obligate OHRB, often harbour multiple putative reductive dehalogenase genes (rdhA), most of which have yet to be characterized. We recently sequenced and closed the genomes of eight new strains, increasing the number of available D. mccartyi genomes in NCBI from 16 to 24. From all available OHRB genomes, we classified predicted translations of reductive dehalogenase genes using a previously established 90% amino acid pairwise identity cut-off to identify Ortholog Groups (OGs). Interestingly, the majority of D. mccartyi dehalogenase gene sequences, once classified into OGs, exhibited a remarkable degree of synteny (gene order) in all genomes sequenced to date. This organization was not apparent without the classification. A high degree of synteny indicates that differences arose from rdhA gene loss rather than recombination. Phylogenetic analysis suggests that most rdhA genes have a long evolutionary history in the Dehalococcoidia with origin prior to speciation of Dehalococcoides and Dehalogenimonas. We also looked for evidence of synteny in the genomes of other species of OHRB. Unfortunately, there are too few closed Dehalogenimonas genomes to compare at this time. There is some partial evidence for synteny in the Dehalobacter restrictus genomes, but here too more closed genomes are needed for confirmation. Interestingly, we found that the rdhA genes that encode enzymes that catalyze dehalogenation of industrial pollutants are the only rdhA genes with strong evidence of recent lateral transfer - at least in the genomes examined herein. Given the utility of the RdhA sequence classification to comparative analyses, we are building a public web server () for the community to use, which allows users to add and classify new sequences, and download the entire curated database of reductive dehalogenases.


Biochemical responses of the copepod Centropages tenuiremis to CO(2)-driven acidified seawater.
An ecophysiological experiment was conducted to examine the biochemical effects of acidified seawater containing elevated concentration of CO(2) (C(CO2) 0.08, 0.20, 0.50 and 1.00%) on the copepod Centropages tenuiremis. AchE, ATPase, SOD, GPx, GST, GSH level and GSH/GSSG ratio of the copepod were analyzed. The results showed that elevated C(CO2) and the duration of culture time significantly influenced several biochemical indices in C. tenuiremis (ATPase, GPx, GST, GSH and SOD). Furthermore, the principal component analysis results indicated that 72.32% of the overall variance was explained by the first three principal components (GPx, SOD and GSH). Changes in GPx and GSH levels may play a significant role in the antioxidant defense of copepods against seawater acidification. The long-term response of copepods to seawater acidification and the synergistic effects of acidification with other environmental factors, such as temperature, salinity and trace metal need further investigation.


Efficacy of heavy eccentric calf training for treating mid-portion Achilles tendinopathy: a systematic review and meta-analysis.
To assess the effectiveness of heavy eccentric calf training (HECT) in comparison with natural history, traditional physiotherapy, sham interventions or other exercise interventions for improvements in pain and function in mid-portion Achilles tendinopathy. A systematic review and meta-analysis were conducted as per the PRISMA guidelines. PUBMED, CINAHL (Ovid) and CINAHL (EBSCO) were searched from inception until 24 September 2018. Randomised controlled trials comparing HECT to natural history, sham exercise, traditional physiotherapy and other exercise interventions were included. Primary outcome assessing pain and function was the Victorian Institute of Sports Assessment-Achilles. Seven studies met the inclusion criteria. This review suggests HECT may be superior to both natural history, mean difference (MD) (95% CI) of 20.6 (11.7 to 29.5, one study) and traditional physiotherapy, MD (95% CI) of 17.70 (3.75 to 31.66, two studies). Following removal of one study, at high risk of bias, due to pre-planned sensitivity analysis, this review suggests HECT may be inferior to other exercise interventions, MD (95% CI) of -5.65 (-10.51 to -0.79, three studies). However, this difference is unlikely to be clinically significant. Current evidence suggests that HECT may be superior to natural history and traditional physiotherapy while HECT may be inferior to other exercise interventions. However, due to methodological limitations, small sample size and a lack of data we are unable to be confident in the results of the estimate of the effect, as the true effect is likely to be substantially different. PROSPERO registration number: CRD4201804493 PROTOCOL REFERENCE: This protocol has been published open access: Murphy M, Travers MJ, Gibson, W. Is heavy eccentric calf training superior to natural history, sham rehabilitation, traditional physiotherapy and other exercise interventions for pain and function in mid-portion Achilles tendinopathy? Systematic Reviews 2018; 7: 58.


Children's experiences of domestic violence and abuse: Siblings' accounts of relational coping.
This article explores how children see their relationships, particularly their sibling relationships, in families affected by domestic violence (DV) and how relationality emerges in their accounts as a resource to build an agentic sense of self. The 'voice' of children is largely absent from the DV literature, which typically portrays them as passive, damaged and relationally incompetent. Children's own understandings of their relational worlds are often overlooked, and consequently, existing models of children's social interactions give inadequate accounts of their meaning-making-in-context. Drawn from a larger study of children's experiences of DV and abuse, this article uses two case studies of sibling relationships to explore young people's use of relational resources, for coping with violence in the home. The article explores how relationality and coping intertwine in young people's accounts and disrupts the taken-for-granted assumption that children's 'premature caring' or 'parentification' is (only) pathological in children's responses to DV. This has implications for understanding young people's experiences in the present and supporting their capacity for relationship building in the future.


AH jump duration is associated with elimination of slow pathway during ablation of atrioventricular nodal reentrant tachycardia.
Ablating the slow pathway (SP) is the superior treatment for atrioventricular nodal reentrant tachycardia (AVNRT) with a low complication rate. However, the ablation of the SP could result in either complete elimination or modification of the SP. We aimed to investigate whether the duration of AH jump pre-ablation associated with the outcome of elimination of SP. We included 56 patients with typical AVNRT (slow-fast), 20 males and 36 females, aged 44.2 ± 15.1 years. Slow pathway ablation was performed using classical approach. Univariate and multivariate analysis was performed for potential predictors of SP elimination. Typical AVNRT was inducible in all patients. Post-ablation, non-inducibility of AVNRT was obtained in all 56 (100%) patients, with SP elimination in 33 (61%) patients and SP modification in 23 (39%) patients. Patients with SP elimination had significantly longer AH jump than patients with SP modification. Cox regression analysis showed that AH jump duration was the independent predictor of SP elimination, in which every 20 ms increase in AH jump duration was associated with 1.30 higher rate of SP elimination. Furthermore, ROC curve analysis indicated that the AH jump duration of ≥100 ms had 6.14 times higher probability for complete elimination of the SP with a sensitivity of 79%, specificity of 70%, PPV of 79% and NPV of 70%. AH jump duration pre-ablation is associated with complete elimination of slow pathway during AVNRT ablation.


Nonsyndromic Juvenile Myelomonocytic Leukemia With PTPN11 Mutation in a 9-Year-old Girl.
A 9.5-year-old girl with malaise, fever, massive hepatosplenomegaly, anemia, leukocytosis (37.9 × 10(9)/L), monocytosis (1.48 × 10(9)/L), and thrombocytopenia is presented. Hemoglobin F was increased (18%). Bone marrow erythroid/myeloid ratio was 40/1 with 7% myeloblast and 5% monocyte suggesting erythroleukemia or juvenile myelomonocytic leukemia (JMML). The patient had a fulminant course with respiratory compromise and died in 2 weeks before heterozygous somatic mutation in the PTPN11 gene was shown. JMML must be considered also in the patients older than 6 years. A cytopenic phase may precede JMML. Leucocytosis may be transient and there may be predominance of erythroid precursors in the bone marrow.


Postexposure immunoprophylaxis against B virus (Herpesvirus simiae) infection.
Local infiltration of antiserum into sites inoculated with B virus protected rabbits from an otherwise fatal encephalomyelitis. Treatment was effective when delayed for six hours but not after 24 hours. Homologous rabbit antisera were more effective than heterologous monkey antisera, and protection was unrelated to neutralisation titres. Protection apparently depended not on neutralisation of inoculated virus but on destruction of infected cells before they produced progeny virus. Normal human immunoglobulin able to neutralise B virus did not protect. Intravenously administered antibody was effective only if large doses were given. The findings suggest that persons bitten or scratched by monkeys latently infected with B virus may be treated successfully by immunoprophylaxis with specific antibody. Stocks of human or of more readily available simian antisera should be held in laboratories where such animals are used.


Confusion over live/dead stainings for the detection of vital microorganisms in oral biofilms--which stain is suitable?
There is confusion over the definition of the term "viability state(s)" of microorganisms. "Viability staining" or "vital staining techniques" are used to distinguish live from dead bacteria. These stainings, first established on planctonic bacteria, may have serious shortcomings when applied to multispecies biofilms. Results of staining techniques should be compared with appropriate microbiological data. Many terms describe "vitality states" of microorganisms, however, several of them are misleading. Authors define "viable" as "capable to grow". Accordingly, staining methods are substitutes, since no staining can prove viability.The reliability of a commercial "viability" staining assay (Molecular Probes) is discussed based on the corresponding product information sheet: (I) Staining principle; (II) Concentrations of bacteria; (III) Calculation of live/dead proportions in vitro. Results of the "viability" kit are dependent on the stains' concentration and on their relation to the number of bacteria in the test. Generally this staining system is not suitable for multispecies biofilms, thus incorrect statements have been published by users of this technique.To compare the results of the staining with bacterial parameters appropriate techniques should be selected. The assessment of Colony Forming Units is insufficient, rather the calculation of Plating Efficiency is necessary. Vital fluorescence staining with Fluorescein Diacetate and Ethidium Bromide seems to be the best proven and suitable method in biofilm research.Regarding the mutagenicity of staining components users should be aware that not only Ethidium Bromide might be harmful, but also a variety of other substances of which the toxicity and mutagenicity is not reported. - The nomenclature regarding "viability" and "vitality" should be used carefully.- The manual of the commercial "viability" kit itself points out that the kit is not suitable for natural multispecies biofilm research, as supported by an array of literature.- Results obtained with various stains are influenced by the relationship between bacterial counts and the amount of stain used in the test. Corresponding vitality data are prone to artificial shifting.- As microbiological parameter the Plating Efficiency should be used for comparison.- Ethidium Bromide is mutagenic. Researchers should be aware that alternative staining compounds may also be or even are mutagenic.


Comparing the Graphical Features of Simple Artificial Neural Networks and Cortical Development.
Brain development is characterized by changes in connections and information processing complexity. These changes inspire the training process of artificial neural network (ANN), which requires adjusting the neuron weights and biases to enhance efficiency in performing a specific task. In this work, we found affinities in the ratio of positive and negative weights in simple ANNs during training with that of excitatory and inhibitory synapses in the cortex. Additionally, we present a graphical representation of simple ANNs formed by pruning unimportant weights and aligning neurons and connections of different layers. Our findings suggest a strong relationship between the accuracy of simple neural network and graphical representation features, with graphical features at the inflection point resembling the graphical representation of the cortex.


Nicotine-induced hyperlocomotion is not modified by the estrous cycle, ovariectomy and estradiol replacement at physiological level.
The present study was designed to investigate whether nicotine's effect on locomotion might be modulated by the ovarian hormone at physiological level. Rats at normal cycling of estrus and diestrus were selected for the comparison of nicotine-induced hyperlocomotion based on the document that the release of striatal dopamine was greatest at the estrous phase. Ovariectomized rats primed with or without estrogen at physiological level were also selected for comparison. Increase in spontaneous locomotion by nicotine was statistically significant at the doses of 0.15 and 0.3 mg/kg (p < 0.001). The stimulating effect of nicotine led the locomotor response to almost the same magnitude in all hormonal groups studied. Nicotine-induced hyperlocomotion appeared to be mediated by central nicotinic receptor because it was blocked by mecamylamine (0.5 and 1.0 mg/kg, i.p.). Also it was blocked by haloperidol (0.04 and 0.08 mg/kg, i.p.) indicating the involvement of dopaminergic neurotransmission. These effects were similar in all groups regardless of the estrous cycle or ovariectomy. The observed data provided behavioral evidence to suggest that the effect of nicotine on locomotion-related dopaminergic neurons might not be modified by the physiological action of estrogen.


The novel sphingosine 1-phosphate receptor AGR16 is coupled via pertussis toxin-sensitive and -insensitive G-proteins to multiple signalling pathways.
In the present study, we determined the agonist specificity and the signalling mechanisms of a putative sphingosine 1-phosphate (S1P) receptor, AGR16. In CHO cells transiently transfected with an AGR16 expression vector, but not in cells transfected with an empty vector, the addition of a low concentration of S1P (1 nM) caused an increase in the intracellular free Ca2+ concentration ([Ca2+]i) by mobilization of Ca2+ from both intra- and extra-cellular pools. To determine the spectrum of agonists for AGR16, we employed K562 cells, which in the naive state do not respond at all to either S1P or structurally related lipids with an increase in [Ca2+]i. In K562 cells stably expressing AGR16, S1P and sphingosylphosphorylcholine (SPC) dose-dependently increased [Ca2+]i with half-maximal values of 3 nM and 100 nM respectively. In CHO cells stably expressing AGR16 (CHO-AGR16), but not in parental CHO cells, we observed specific binding of [32P]S1P, which was displaced by unlabelled S1P and SPC. In CHO-AGR16 cells, but not in parental CHO cells, S1P stimulated the production of inositol phosphates and Ca2+ mobilization which was only 30% inhibited by pertussis toxin (PTX), different from the case of the recently identified S1P receptor EDG1. Also in CHO-AGR16 cells, but not in CHO cells, S1P at higher concentrations activated mitogen-activated protein kinase (MAPK) in a PTX-sensitive and Ras-dependent manner. S1P also induced the activation of two stress-activated MAPKs, c-Jun N-terminal kinase and p38, in a manner that was totally insensitive to PTX. In CHO-AGR16 cells, S1P induced stress-fibre formation, with an increase in myosin light chain phosphorylation, in a PTX-insensitive and Rho-dependent manner. S1P also induced an increase in the cellular cAMP content in CHO-AGR16 cells, which contrasts sharply with the case of EDG1. These results establish that the S1P receptor AGR16 is coupled via both PTX-sensitive and -insensitive G-proteins to multiple effector pathways.


DFT study of the structures and energetics of 98-atom AuPd clusters.
The energetics, structures and segregation of 98-atom AuPd nanoclusters are investigated using a genetic algorithm global optimization technique with the Gupta empirical potential (comparing three different potential parameterisations) followed by local minimizations using Density Functional Theory (DFT) calculations. A shell optimization program algorithm is employed in order to study the energetics of the highly symmetric Leary Tetrahedron (LT) structure and optimization of the chemical ordering of a number of structural motifs is carried out using the Basin Hopping Monte Carlo approach. Although one of the empirical potentials is found to favour the LT structure, it is shown that Marks Decahedral and mixed FCC-HCP motifs are lowest in energy at the DFT level.


Incidence of associated events during the performance of invasive procedures in healthy human volunteers.
Metabolic investigations often utilize arteriovenous sampling and muscle biopsy. These investigations represent some risk to the subject. We examined 369 studies performed in the General Clinical Research Center between January 1994 and May 2003 for events related to femoral catheterization and muscle biopsies. Incidents were further examined by age (younger: 18-59 yr, n=133; and older: 60-76 yr, n=28). There were no clinically defined major complications associated with either procedure. The incidence of femoral catheter repositioning or reinsertion was higher in the older group (25.5 vs. 9.7%). There was no difference in the incidence of premature removal of catheters, ecchymosis or hematoma, or the persistence of pain after discharge. The occurrence of all incidents did not increase with multiple catheterizations. Muscle biopsy was associated with infrequent ecchymosis or hematoma in both groups (1.1 and 3.6% in younger and older groups, respectively). Both procedures entail a small likelihood of a vagallike response (3.3% overall), resulting in nausea, dizziness, and rarely a loss of consciousness. These results indicate that, in skilled hands and a defined clinical setting, the incidents associated with femoral catheterization and muscle biopsy in healthy volunteers are reasonable and largely controllable.


Low Burden Strategies Are Needed to Reduce Smoking in Rural Healthcare Settings: A Lesson from Cancer Clinics.
Rural populations face significant smoking-related health disparities, such as a higher prevalence of lung cancer and cancer mortality, higher prevalence of smoking, and lower likelihood of receiving cessation treatment than urban counterparts. A significant proportion of health disparities in rural populations could be eliminated with low-barrier, easy-access treatment delivery methods for smoking cessation. In this study, we assessed treatment engagement among patients in rural and urban settings. Then, we examined the effect of an electronic health record-based smoking cessation module on patient receipt of evidence-based cessation care. As part of a quality improvement project, we retrospectively observed 479,798 unique patients accounting for 1,426,089 outpatient clinical encounters from June 2018-March 2019 across 766 clinics in the greater St. Louis, southern Illinois, and mid-Missouri regions. Smoking prevalence was higher in rural versus urban clinics (20.7% vs. 13.9%, 6.7% [6.3, 7.1], odds ratio = 1.6 [1.6, 1.6], p < 0.0001), and yet rural smokers were nearly three times less likely than their urban counterparts to receive any smoking cessation treatment after adjusting for patients clustering within clinics (9.6% vs. 25.8%, -16.2% [-16.9, -15.5], odds ratio = 0.304 [0.28, 0.33], p < 0.0001). Although not yet scaled up in the rural setting, we examined the effects of a low-burden, point-of-care smoking module currently implemented in cancer clinics. After adjusting for patient clustering within clinics, patients were more likely to receive smoking treatment in clinics that implemented the module versus clinics that did not implement the module (31.2% vs. 17.5%, 13.7% [10.8, 16.6], odds ratio = 2.1 [1.8, 2.6], p < 0.0001). The point-of-care treatment approach offers a promising solution for rural settings, both in and outside the context of cancer care.


The Optimum Power Load: A Simple and Powerful Tool for Testing and Training.
The optimal power load is defined as the load that maximizes power output in a given exercise. This load can be determined through the use of various instruments, under different testing protocols. Specifically, the "optimum power load" (OPL) is derived from the load-velocity relationship, using only bar force and bar velocity in the power computation. The OPL is easily assessed using a simple incremental testing protocol, based on relative percentages of body mass. To date, several studies have examined the associations between the OPL and different sport-specific measures, as well as its acute and chronic effects on athletic performance. The aim of this brief review is to present and summarize the current evidence regarding the OPL, highlighting the main lines of research on this topic and discussing the potential applications of this novel approach for testing and training. The validity and simplicity of OPL-based schemes provide strong support for their use as an alternative to more traditional strength-power training strategies. The OPL method can be effectively used by coaches and sport scientists in different sports and populations, with different purposes and configurations.


Inhibitory CD8+ T cells in autoimmune disease.
Rheumatologists have long been focused on developing novel immunotherapeutic agents to manage such prototypic autoimmune diseases as rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). The ultimate challenge in providing immunosuppressive treatment for patients with RA and SLE has derived from the dilemma that both protective and harmful immune responses result from adaptive immune responses, mediated by highly diverse, antigen-specific T and B cells endowed with powerful effector functions and the ability for long-lasting memory. As regulatory/suppressor T cells can suppress immunity against any antigen, including self-antigens, they emerge as an ideal therapeutic target. Several distinct subtypes of CD8(+) suppressor cells (Ts) have been described that could find application in treating RA or SLE. In a xenograft model of human synovium, CD8(+)CD28(-)CD56(+) T cells effectively suppressed rheumatoid inflammation. Underlying mechanisms involve conditioning of antigen presenting cells (APC). Adoptively transferred CD8(+) T cells characterized by IL-16 secretion have also exhibited disease-inhibitory effects. In mice with polyarthritis, CD8(+) Ts suppressed inflammation by IFNgamma-mediated modulation of the tryptophan metabolism in APC. In SLE animal models, CD8(+) Ts induced by a synthetic peptide exerted suppressive activity mainly via the TGFbeta-Foxp3-PD1 pathway. CD8(+) Ts induced by histone peptides were found to downregulate disease activity by secreting TGFbeta. In essence, disease-specific approaches may be necessary to identify CD8(+) Ts optimally suited to treat immune dysfunctions in different autoimmune syndromes.


Research progress of CXCR3 inhibitors.
The human CXCR3 receptor was initially identified and cloned in the mid-1990s. In the process of understanding CXCR3, it gradually found that it plays an important role in the process of a variety of diseases, including inflammation, immune diseases, cancer, cardiovascular diseases, central nervous system diseases, etc., which attracted the attention of many researchers. Subsequently, some small molecule inhibitors targeting CXCR3 receptors were also developed. Unfortunately, no CXCR3 inhibitors have been approved for marketing by FDA. Up to now, only one CXCR3 small molecule inhibitor has entered the clinical trial stage, but it has not achieved ideal results in the end. Therefore, there is still much to think about and explore for the development of CXCR3 inhibitors. This article reviews the important role of CXCR3 in various physiological and pathological processes and some small molecule inhibitors of CXCR3.


Menaquinone biosynthesis: formation of aminofutalosine requires a unique radical SAM enzyme.
Menaquinone (MK, vitamin K2) is a lipid-soluble molecule that participates in the bacterial electron transport chain. In mammalian cells, MK functions as an essential vitamin for the activation of various proteins involved in blood clotting and bone metabolism. Recently, a new pathway for the biosynthesis of this cofactor was discovered in Streptomyces coelicolor A3(2) in which chorismate is converted to aminofutalosine in a reaction catalyzed by MqnA and an unidentified enzyme. Here, we reconstitute the biosynthesis of aminofutalosine and demonstrate that the missing enzyme (aminofutalosine synthase, MqnE) is a radical SAM enzyme that catalyzes the addition of the adenosyl radical to the double bond of 3-[(1-carboxyvinyl)oxy]benzoic acid. This is a new reaction type in the radical SAM superfamily.


Improving the cost, quality, and safety of perioperative care: A systematic review of the literature on implementation of the perioperative surgical home.
The perioperative surgical home (PSH) is a recent innovation in perioperative care delivery that coordinates the pre-, intra-, and post-operative elements of surgical care under one organizational umbrella. Although significant research supports the efficacy of individual elements of the PSH in improving outcomes, there is not a published systematic review of the efficacy of entire PSH programs in improving patient outcomes. This article summarizes descriptions of PSH programs available in the literature and examines outcomes of original studies of PSH implementation. We conducted a systematic literature review to identify relevant articles on PSH implementation and synthesize our findings. The studies included in our review took place at multiple academic and community hospitals in the United States. Patients involved in the PSH studies included surgical patients of various ages and ASA classifications in various surgical specialties. All studies included in our review involved the implementation of a PSH program. Outcomes examined include length of stay, postoperative recovery, readmission rates, and patient discharge destination, among others. We identified 11 studies of PSH implementation that met our inclusion and exclusion criteria. Most PSH programs described in these studies included an emphasis on preoperative education, standardization of care protocols in all phases of surgery, use of opioid-sparing multimodal analgesia, and collaborative staffing models. PSH program implementation was often associated with decreased length of stay, decreased utilization of postoperative opioids, decreased utilization of the ICU, and increased probability of discharge to home. PSH implementation was not meaningfully associated with reductions in readmission rates. Findings for cost reductions following PSH implementation were mixed. Early evidence indicates that through elements that emphasize care coordination, standardization, and patient-centeredness, PSH programs can improve patient postoperative recovery outcomes and decrease hospital utilization.


Analytical Prediction of Gas Permeation through Graphene Nanopores of Varying Sizes: Understanding Transitions across Multiple Transport Regimes.
Nanoporous graphene is a promising candidate material for gas separation membranes, due to its atomic thickness and low cross-membrane transport resistance. The mechanisms of gas permeation through graphene nanopores, in both the large and small pore size limits, have been reported in the literature. However, mechanistic insights into the crossover from the small pore size limit to the large pore size limit are still lacking. In this study, we develop a comprehensive theoretical framework to predict gas permeance through graphene nanopores having a wide range of diameters using analytical equations. We formulate the transport kinetics associated with the direct impingement from the bulk and with the surface diffusion from the adsorption layer on graphene and then combine them to predict the overall gas permeation rate using a reaction network model. We also utilize molecular dynamics simulations to validate and calibrate our theoretical model. We show that the rates of both the direct impingement and the surface diffusion pathways need to be corrected using different multiplicative factors, which are functions of temperature, gas kinetic diameter, and pore diameter. Further, we find a minor spillover pathway that originates from the surface adsorption layer, but is not included in our theoretical model. Finally, we utilize the corrected model to predict the permeances of CO2, CH4, and Ar through graphene nanopores. We show that as the pore diameter increases, gas transport through graphene nanopores can transition from being translocation dominated (pore diameter < 0.7 nm), to surface pathway dominated (pore diameter 1-2 nm), and finally to direct pathway dominated (pore diameter > 4 nm). The various gas permeation mechanisms outlined in this study will be particularly useful for the rational design of membranes made out of two-dimensional materials such as graphene for gas separation applications.


[Irreversible pH-denaturation of tissue thromboplastin].
Irreversible denaturation of tissue thromboplastin from human brain occurred at pH values below 5.0 and above 11.0. Coagulating activity of total phospholipid fraction of thromboplastin was decreased after incubation in acid or alkaline media.


Nuclear and mitochondrial DNA alterations in newborns with prenatal exposure to cigarette smoke.
Newborns exposed to maternal cigarette smoke (CS) in utero have an increased risk of developing chronic diseases, cancer, and acquiring decreased cognitive function in adulthood. Although the literature reports many deleterious effects associated with maternal cigarette smoking on the fetus, the molecular alterations and mechanisms of action are not yet clear. Smoking may act directly on nuclear DNA by inducing mutations or epigenetic modifications. Recent studies also indicate that smoking may act on mitochondrial DNA by inducing a change in the number of copies to make up for the damage caused by smoking on the respiratory chain and lack of energy. In addition, individual genetic susceptibility plays a significant role in determining the effects of smoking during development. Furthermore, prior exposure of paternal and maternal gametes to cigarette smoke may affect the health of the developing individual, not only the in utero exposure. This review examines the genetic and epigenetic alterations in nuclear and mitochondrial DNA associated with smoke exposure during the most sensitive periods of development (prior to conception, prenatal and early postnatal) and assesses how such changes may have consequences for both fetal growth and development.